Assessment of myocardial perfusion is a gatekeeper diagnostic exam that has high sensitivity for identifying individuals with ischemic heart disease. Millions of perfusion studies are performed annually in the US using a stress/rest paradigm with a radioactive tracer followed by nuclear imaging. While this is an effective exam, it involves delivering a dose of ionizing radiation to the patient and the spatial resolution of the technique s rather low which limits detection of smaller or subendocardial perfusion defects. Cardiovascular magnetic resonance imaging (CMR) is considered a competitive first-line test for common indications such as the evaluation of ischemic heart disease. CMR involves no radiation and has an order of magnitude higher spatial resolution than nuclear techniques. CMR can assess both myocardial perfusion and infarction with independent techniques in a single session. However current CMR assessment of perfusion involves adenosine-stress of the patient while in the scanner and rapid imaging to assess perfusion of first pass of the MR contrast agent. With this project, we aim to develop a technique that allows high quality, prolonged visualization of myocardial perfusion, using CM-65, a novel MR imaging agent targeted to type I collagen. We have shown in preliminary studies in pigs that CM-65 can be administered during stress (hyperemia) and identify perfusion defects in the heart even after stress is ceased. In Phase I of the study, we will develop a clinically feasible CM-65 stress perfusion protocol in a large animal model that can be directly adapted for use in humans. In Phase II, we will test the optimized clinically, feasible CM-65 protocol across a range of flow reduction with and without myocardial infarction in large animal models. We will also address several of the safety and pharmacokinetic studies required for IND submission. Together, these data will form the basis for an IND submission for clinical testing of CM-65 enhanced MR in the context of ischemic heart disease.